2yvq

Structural highlights

Disease

[CPSM_HUMAN] Defects in CPS1 are the cause of carbamoyl phosphate synthetase 1 deficiency (CPS1D) [MIM:237300]. CPS1D is an autosomal recessive disorder of the urea cycle causing hyperammonemia. Clinical features include protein intolerance, intermittent ataxia, seizures, lethargy, developmental delay and mental retardation.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]} Note=Genetic variations in CPS1 influence the availability of precursors for nitric oxide (NO) synthesis and play a role in clinical situations where endogenous NO production is critically important, such as neonatal pulmonary hypertension, increased pulmonary artery pressure following surgical repair of congenital heart defects or hepatovenocclusive disease following bone marrow transplantation. Infants with neonatal pulmonary hypertension homozygous for Thr-1406 have lower L-arginine concentrations than neonates homozygous for Asn-1406.^[13]

Function

[CPSM_HUMAN] Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Carbamoyl phosphate synthetase

References

1. ↑ Finckh U, Kohlschutter A, Schafer H, Sperhake K, Colombo JP, Gal A. Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1. Hum Mutat. 1998;12(3):206-11. PMID:9711878 doi:<206::AID-HUMU8>3.0.CO;2-E 10.1002/(SICI)1098-1004(1998)12:3<206::AID-HUMU8>3.0.CO;2-E
2. ↑ Funghini S, Donati MA, Pasquini E, Zammarchi E, Morrone A. Structural organization of the human carbamyl phosphate synthetase I gene (CPS1) and identification of two novel genetic lesions. Hum Mutat. 2003 Oct;22(4):340-1. PMID:12955727 doi:http://dx.doi.org/10.1002/humu.9184
3. ↑ Haberle J, Schmidt E, Pauli S, Rapp B, Christensen E, Wermuth B, Koch HG. Gene structure of human carbamylphosphate synthetase 1 and novel mutations in patients with neonatal onset. Hum Mutat. 2003 Apr;21(4):444. PMID:12655559 doi:10.1002/humu.9118
4. ↑ Rapp B, Haberle J, Linnebank M, Wermuth B, Marquardt T, Harms E, Koch HG. Genetic analysis of carbamoylphosphate synthetase I and ornithine transcarbamylase deficiency using fibroblasts. Eur J Pediatr. 2001 May;160(5):283-7. PMID:11388595
5. ↑ Aoshima T, Kajita M, Sekido Y, Kikuchi S, Yasuda I, Saheki T, Watanabe K, Shimokata K, Niwa T. Novel mutations (H337R and 238-362del) in the CPS1 gene cause carbamoyl phosphate synthetase I deficiency. Hum Hered. 2001;52(2):99-101. PMID:11474210 doi:53360
6. ↑ Wakutani Y, Nakayasu H, Takeshima T, Adachi M, Kawataki M, Kihira K, Sawada H, Bonno M, Yamamoto H, Nakashima K. Mutational analysis of carbamoylphosphate synthetase I deficiency in three Japanese patients. J Inherit Metab Dis. 2004;27(6):787-8. PMID:15617192
7. ↑ Haberle J, Koch HG. Genetic approach to prenatal diagnosis in urea cycle defects. Prenat Diagn. 2004 May;24(5):378-83. PMID:15164414 doi:10.1002/pd.884
8. ↑ Eeds AM, Hall LD, Yadav M, Willis A, Summar S, Putnam A, Barr F, Summar ML. The frequent observation of evidence for nonsense-mediated decay in RNA from patients with carbamyl phosphate synthetase I deficiency. Mol Genet Metab. 2006 Sep-Oct;89(1-2):80-6. Epub 2006 Jun 5. PMID:16737834 doi:10.1016/j.ymgme.2006.04.006
9. ↑ Kurokawa K, Yorifuji T, Kawai M, Momoi T, Nagasaka H, Takayanagi M, Kobayashi K, Yoshino M, Kosho T, Adachi M, Otsuka H, Yamamoto S, Murata T, Suenaga A, Ishii T, Terada K, Shimura N, Kiwaki K, Shintaku H, Yamakawa M, Nakabayashi H, Wakutani Y, Nakahata T. Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiency. J Hum Genet. 2007;52(4):349-54. Epub 2007 Feb 20. PMID:17310273 doi:10.1007/s10038-007-0122-9
10. ↑ Pekkala S, Martinez AI, Barcelona B, Yefimenko I, Finckh U, Rubio V, Cervera J. Understanding carbamoyl-phosphate synthetase I (CPS1) deficiency by using expression studies and structure-based analysis. Hum Mutat. 2010 Jul;31(7):801-8. doi: 10.1002/humu.21272. PMID:20578160 doi:10.1002/humu.21272
11. ↑ Moonen RM, Reyes I, Cavallaro G, Gonzalez-Luis G, Bakker JA, Villamor E. The T1405N carbamoyl phosphate synthetase polymorphism does not affect plasma arginine concentrations in preterm infants. PLoS One. 2010 May 25;5(5):e10792. doi: 10.1371/journal.pone.0010792. PMID:20520828 doi:10.1371/journal.pone.0010792
12. ↑ Haberle J, Shchelochkov OA, Wang J, Katsonis P, Hall L, Reiss S, Eeds A, Willis A, Yadav M, Summar S, Lichtarge O, Rubio V, Wong LJ, Summar M. Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations. Hum Mutat. 2011 Jun;32(6):579-89. doi: 10.1002/humu.21406. Epub 2011 May 5. PMID:21120950 doi:10.1002/humu.21406
13. ↑ Moonen RM, Reyes I, Cavallaro G, Gonzalez-Luis G, Bakker JA, Villamor E. The T1405N carbamoyl phosphate synthetase polymorphism does not affect plasma arginine concentrations in preterm infants. PLoS One. 2010 May 25;5(5):e10792. doi: 10.1371/journal.pone.0010792. PMID:20520828 doi:10.1371/journal.pone.0010792